A kinase-dead knock-in mutation in mTOR leads to early embryonic lethality and is dispensable for the immune system in heterozygous mice.

ABSTRACT:

Background

The mammalian target of rapamycin protein (mTOR) is an evolutionarily conserved kinase that regulates protein synthesis, cell cycle progression and proliferation in response to various environmental cues. As a critical downstream mediator of PI3K signaling, mTOR is important for lymphocyte development and function of mature T and B-cells. Most studies of mTOR in immune responses have relied on the use of pharmacological inhibitors, such as rapamycin. Rapamycin-FKBP12 complex exerts its immunosuppressive and anti-proliferative effect by binding outside the kinase domain of mTOR, and subsequently inhibiting downstream mTOR signaling.

Results

To determine the requirement for mTOR kinase activity in the immune system function, we generated knock-in mice carrying a mut

SUBMITTER: Shor B 

PROVIDER: S-EPMC2698930 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature